Assessment of glucose kinetics with real-time continuous glucose monitoring during labor.

AIM: Changes in glucose levels during labor have not been sufficiently investigated in pregnant women. Using real-time continuous glucose monitoring, we aimed to assess glucose kinetics during labor among pregnant women with gestational diabetes mellitus (PwGDM), and those with normal glucose tolerance (PwNGT). METHODS: Japanese PwGDM and PwNGT who had planned a transvaginal delivery at Okayama University Hospital were enrolled. The correlation between changes in glucose levels during labor among the PwGDM and PwNGT groups at four time periods was assessed: (i) active phase of 1st stage of labor; (ii) 2nd stage of labor; (iii) postpartum 0-12 h; and (iv) postpartum 12-48 h. RESULTS: In total, 18 and 22 PwGDM and PwNGT, respectively, were enrolled. During labor, both groups had similar changes in glucose levels over time, which peaked during period 3. The main effect of glucose level changes was the labor period (P < 0.001), not the presence of gestational diabetes mellitus. Furthermore, differences in glucose levels in the PwGDM group were observed between periods 1 and 2 (P = 0.037), 1 and 3 (P = 0.024), 3 and 4 (P = 0.005); differences in glucose levels in the PwNGT group were observed between periods 3 and 4 (P = 0.024). CONCLUSION: During labor, both PwGDM and PwNGT groups showed similar changes in glucose levels over time. During delivery, the PwGDM who regularly measured their own glucose levels could be managed using the same nutritional management methods as those for PwNGT.

Successful Delivery after Abdominal Radical Trachelectomy, Using Transabdominal Cerclage in Early Pregnancy.

Radical trachelectomy (RT) is a fertility-sparing surgery for cervical cancer. Postoperative pregnancies have a high risk of abortion and prematurity. To prevent this, a procedure involving transabdominal cerclage (TAC) was devised for shortened cervical canals post-RT. Here we describe the successful management of a pregnancy after abdominal RT (ART). The 34-year-old patient was gravida 1, para 0. When she was 27, she underwent ART for stage Ib1 cervical cancer, and she became pregnant 7 years later. Because her cervical canal was 16.7 mm during early pregnancy, we performed TAC at 12 weeks of pregnancy. Post-surgery, we administered an infusion of ritodrine hydrochloride for tocolysis. A selective caesarean section was performed at 36 weeks, with the delivery of a healthy infant.

Relationship between Intracellular Signaling of the (Pro)renin Receptor and the Pathogenesis of Preeclampsia.

An association between preeclampsia and (pro)renin was recently reported. Intracellular signaling of the (pro) renin receptor [(P)RR] increases the expressions of TGF-ß and PAI-1. In this study we sought to clarify the involvement of (pro)renin in the pathogenesis of preeclampsia via the intracellular signaling of (P)RR on preeclampsia placentas. Activated (pro)renin plasma concentrations were compared between pregnant women with (n=15) and without (n=28) preeclampsia. The placentas were immunohistochemically evaluated with anti-HIF-1α and anti-(P)RR antibodies. HTR-8/SVneo cells were cultured under hypoxic conditions and treated with human recombinant (pro)renin. The mRNA expressions of HIF-1α, (P)RR, PAI-1, TGF-ß, and ET-1 were also examined by real-time RCR. The activated (pro)renin plasma concentration was significantly higher in the third vs. the second trimester in the preeclampsia patients. HIF-1α and (P)RR expressions were significantly increased in the preeclampsia placentas. The mRNA expressions of PAI-1, TGF-ß, and ET-1 were significantly increased in the experiments using recombinant (pro)renin vs. hypoxic conditions. (P)RR expression in preeclampsia placentas is increased by persistent hypoxia through the second and third trimesters, and PAI-1, TGF-ß, and ET-1 production is increased via (P)RR. Our results suggest that ET-1 production via the intracellular signaling of (P)RR is important in the pathogenesis of preeclampsia.

A Case of Nager Syndrome Diagnosed Before Birth.

Nager syndrome is a rare disease involving severe micrognathia and upper limb shortening. In this report, we describe a case in which micrognathia of the fetus was suspected based on the observation of upper limb shortening during detailed B mode and 3D/4D ultrasonographic observation, and combined fetal MRI and 3D-CT led to a prenatal diagnosis of Nager syndrome. Upon birth, because severe micrognathia caused airway obstruction and made it difficult to spread the larynx for intubation, effective ventilation could not be carried out and a tracheostomy was necessary. Since a differential diagnosis of Nager syndrome can be made based on the fact that micrognathia typically co-occurs with upper limb shortening, it is possible to diagnose the disease before birth and prepare for life-saving measures accordingly.

Upregulation of Angiogenic Factors via Protein Kinase C and Hypoxia-induced Factor-1α Pathways under High-glucose Conditions in the Placenta.

Abnormal glucose metabolism during pregnancy is an established risk factor for preeclampsia (PE). Disruption of the balance between placental angiogenic factors is linked to PE pathophysiology. We examined whether hypoxia-induced factor-1α (HIF-1α) and protein kinase Cß (PKCß) are involved in the regulation of placental angiogenic factors under high-glucose conditions in vitro. The human choriocarcinoma cell lines BeWo and JEG-3, and the human trophoblast cell line HTR-8/SVneo were cultured with 10 and 25 mmol/L glucose [control glucose group (CG) and high-glucose group (HG), respectively]. We examined the changes in HIF-1α, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) expression in the CG and HG by real-time PCR and ELISA. PKC activation was also measured by ELISA. The expressions of HIF-1α, sFlt-1, PlGF, and VEGF were significantly higher in the HG than in the CG. PKC activity was significantly increased in the HG. High glucose affected the expression of angiogenic factors in choriocarcinoma cells via the PKCß and HIF-1α pathways, suggesting their involvement in PE pathogenesis.

Discrepancy between Non-invasive Prenatal Genetic Testing (NIPT) and Amniotic Chromosomal Test due to Placental Mosaicism: A Case Report and Literature Review.

We experienced a case of advanced maternal age in which a fetus was found to be positive for trisomy 18 at re-examination following indeterminate non-invasive prenatal genetic testing (NIPT), the amniotic fluid chromosomal test revealed a normal karyotype, and confined placental mosaicism (CPM) was observed in an SNP microarray analysis of the placenta. The child was born with no defects or complications. In the present case, the result of the original NIPT at week 15 of pregnancy was indeterminate and the subsequent re-examination result was positive; since the definitive normal diagnosis was not reported until the latter half of week 21, the pregnant patient was subjected to psychological stress for a long period of time. The problem with NIPT is that most of the fetus-derived cell-free DNA in the maternal blood is not derived directly from the fetus but from the villus cells of the placenta, leading to indefinite diagnoses; for that reason, the pregnant patient was subjected to psychological stress for a long period of time. Of the 18,251 cases undergoing NIPT in the past 2 years in Japan, 51 had indeterminate results; this was the second case in which a subsequent re-examination gave a positive result for trisomy 18.

Comparison of Kidney Function between Gestational Hypertension and Preeclampsia.

Although gestational hypertension (GH) is thought to be different from preeclampsia (PE), in Japan GH and PE are usually treated as the same disease (i.e., pregnancy-induced hypertension). Here we sought to determine whether there are any differences in fetal growth and maternal kidney function between pregnancies with PE and those with GH. We retrospectively analyzed 61 GH patients and 60 PE patients with singleton pregnancies who delivered at Okayama University Hospital (2008-2015). We compared maternal and perinatal outcomes and maternal kidney function parameters between the GH and PE pregnancies. The mean values of maternal age (p=0.01), gestational age at delivery (p<0.0001), placental weight (p=0.002), birth weight and height (p<0.0001, p=0.0001), and head circumference standard deviation score (p=0.007) of newborns of the GH group were significantly higher than those of the PE group. The duration until termination of PE or GH was not significantly correlated with kidney function. The birth weight percentile was significantly correlated with kidney function in PE but not GH. However, GH patients with poor kidney function and small-for-gestational age infants showed perinatal outcomes similar to those of the PE group. Monitoring kidney function is thus important for determining the severity of PE and GH.

The effects of paternal high-fat diet exposure on offspring metabolism with epigenetic changes in the mouse adiponectin and leptin gene promoters.

Recent studies have demonstrated that epigenetic changes resulting from malnutrition might play important roles in transgenerational links with metabolic diseases. Previously, we observed that exposure to a high-fat diet (HFD) in utero caused a metabolic syndrome-like phenomenon through epigenetic modifications of the adiponectin and leptin genes that persisted for multiple generations. Recent etiological studies indicated that paternal BMI had effects on offspring BMI that were independent of but additive to maternal BMI effects. Thus, we examined whether paternal HFD-induced obesity affected the metabolic status of offspring through epigenetic changes in the adiponectin and leptin genes. Additionally, we investigated whether a normal diet during subsequent generations abolished the epigenetic changes associated with paternal HFD exposure before conception. We observed the effects of paternal HFD exposure before conception over multiple generations on offspring metabolic traits, including weight and fat gain, glucose intolerance, hypertriglyceridemia, abnormal adipocytokine levels, hypertension, and adiponectin and leptin gene expression and epigenetic changes. Normal diet consumption by male offspring during the subsequent generation following paternal HFD exposure diminished whereas consumption for two generations completely abolished the effect of paternal HFD exposure on metabolic traits and adipocytokine promoter epigenetic changes in the offspring. The effects of paternal HFD exposure on offspring were relatively weaker than those following HFD exposure in utero. However, paternal HFD exposure had an additive metabolic effect for two generations, suggesting that both paternal and maternal nutrition might affect offspring metabolism through epigenetic modifications of adipocytokine genes for multiple generations.

A case of subclinical Cushing's syndrome in pregnancy with superimposed preeclampsia.

When we see preexistent hypertension in pregnancy, subclinical Cushing's syndrome should be considered in the differential diagnosis since this disorder can cause perinatal complications. MRI can be useful for identifying adrenal incidental tumors during pregnancy.

A rare maternal gastrointestinal stromal tumor found in the second trimester of pregnancy: A case report.

Gastrointestinal stromal tumors are rare, and in pregnancy they are extremely rare. We present a case of a maternal gastrointestinal stromal tumor found in the second trimester of pregnancy. A 29-year-old woman, gravida 1 para 0, complained of bloody vomiting at 14 weeks of gestation. She had no significant medical history. We performed plain computed tomography and upper gastrointestinal endoscopy. Precise examination revealed a large mass in the stomach and an exposed blood vessel on the surface. An exposed blood vessel can be harmful for mother and fetus as it might rupture during the pregnancy. We performed a distal gastrectomy at 16 weeks of gestation. Histology confirmed a localized gastrointestinal stromal tumor with a high risk of recurrence, and adjuvant imatinib was recommended. The patient elected to delay adjuvant imatinib until after delivery. The postoperative and antenatal course was favorable, and the patient was followed up by ultrasound every 2 months after the operation. After she gave birth at 40 weeks of gestation, she started adjuvant imatinib 400 mg/day. There was no evidence of recurrence 1 year after surgery. There are no guidelines for the management of gastrointestinal stromal tumors in pregnancy. Given the treatment challenges, we believe that pregnant patients should be managed by a multidisciplinary team with expertise in gastrointestinal tumors and fetal-maternal medicine.

Assessment of resting energy expenditure and body composition in Japanese pregnant women with diabetes.

AIMS/INTRODUCTION: To measure longitudinal changes in resting energy expenditure and body composition of Japanese pregnant women with or without diabetes. MATERIALS AND METHODS: The study population consisted of women who had delivered a live singleton neonate after 22 weeks' gestation at Okayama University Hospital from July 2013 to June 2017. Resting energy expenditure and body composition were measured in the first trimester, second trimester, third trimester and postpartum. RESULTS: A total of 144 women participated in this study: 103 with normal glucose tolerance and 41 with diabetes. The resting energy expenditure (kcal/day) of pregnant women with normal glucose tolerance was significantly higher in the third trimester (1,644 ± 234) than in the first (1,461 ± 215) and second trimesters (1,491 ± 219), and postpartum (1,419 ± 254), whereas that of pregnant women with diabetes did not significantly change during all periods (1,568 ± 404, 1,710 ± 332, 1,716 ± 251, 1,567 ± 249). The resting energy expenditure of women with good glycemic control was lower than that of women with poor control. Fat-free mass was closely correlated with resting energy expenditure. CONCLUSIONS: The resting energy expenditure of Japanese pregnant women with normal glucose tolerance was significantly increased in the third trimester. The resting energy expenditure of women with good glycemic control was lower than that of women with poor control. Resting energy expenditure and fat-free mass are potential indexes for medical nutrition therapy in pregnant women with diabetes.

Successful pregnancy located in a uterine cesarean scar: A case report.

Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy. Because CSP carries a high risk of uterine rupture and life-threatening bleeding, the pregnancy should be terminated upon confirmation of diagnosis. There have been few reports of CSP with successful delivery. We present a case of CSP under expectant management, with delivery via planned cesarean section at 35 weeks of gestation. This report suggests that successful pregnancy outcome can be achieved in some women with uterine cesarean scar, but further analysis and additional studies are required in order to describe the optimal protocol of expectant management in CSP.

Sex differences in early growth during the first three years of life in offspring from mothers with pregnancy-induced hypertension.

OBJECTIVES: Newborns born to mothers with pregnancy-induced hypertension (PIH) are thought to be at high risk for lifestyle-related diseases, such as obesity and hypertension, in adulthood. STUDY DESIGN: A longitudinal study of 78 pregnant women with PIH and their newborns, who visited Okayama University Hospital from 2009 to 2013. MAIN OUTCOME MEASURES: We investigated the change in growth of offspring born to mothers with PIH and compared it with the standard growth curve in Japanese to examine whether there was rapid catch-up growth during the first 3years of life. RESULTS: Subjects were 78 pregnant women with PIH and their offspring, who visited Okayama University Hospital from 2009 to 2013. Valid responses were obtained from 29 of 78 (37.1%) women. Body weight and length at birth were at the third percentile or less in females, and at the 10th percentile or less, in males. When body weight and length were compared at 6months, 18months, and 3years old between male and female toddlers, male toddlers slowly caught up until 3years old, but female toddlers rapidly caught up in the first 6months. Furthermore, in newborns with fetal growth restriction caused by the intrauterine environment of PIH, differences in physical development between male and female toddlers were more remarkable. CONCLUSIONS: There is a significant sex difference in catch-up growth during the first 3years, which might be involved in lifestyle-related diseases in adulthood, suggesting continuous follow-up is necessary, especially for female offspring.

Differences in uterine artery blood flow and fetal growth between the early and late onset of pregnancy-induced hypertension.

PURPOSE: We continuously measured bilateral uterine artery (UA) blood flow and compared differences in UA blood flow to investigate the differences in pathophysiology between early- and late-onset pregnancy-induced hypertension (PIH) and the usefulness of continuous monitoring of UA blood flow for the prediction of early-onset PIH. METHODS: The subjects were 76 PIH patients. The mean pulsatility index of bilateral UA (UAPI), an early diastolic notch in the velocity waveform, and regression curves were retrospectively examined and compared between early- and late-onset groups and the groups with and without fetal growth restriction (FGR). RESULTS: Regression curves of the UAPI in the early-onset group persisted at +2.0 standard deviations or more from the second to third trimester, while the UAPI in the late-onset group stayed within the normal range. A significantly higher mean UAPI with a high frequency of an early diastolic notch was observed in the early-onset group compared with the late-onset group in all pregnancy trimesters. There was a significant difference in UA resistance between the mild and severe groups and between the FGR and non-FGR groups, but to a small extent compared with the onset period. CONCLUSION: There was a difference in pathophysiology between early- and late-onset PIH. Continuous monitoring of UA blood flow might be useful for the prediction of early-onset PIH if high UA resistance has been observed.